1. Field of the Invention
This invention relates to an apparatus for an electrode and method used for iontophoresis, and more specifically, to an electrode and method for use of the electrode for iontophoretic transport of an ionic substance transdermally.
2. Background.
Electrodes have been proposed for use in the transdermal delivery of ionic substances. Electromotive force used with an electrode offers the advantage of controlling the rate of delivery. Skin irritation problems occur such as burns at the surface of the skin due to acids or bases formed by electrolysis of the water based medication or electrolyte. Efforts to minimize irritation have been directed to regulating the level of current, improving the electrical connection of the electrode with the skin and reducing the hydrolysis of the water used in the ionic medication and the electrolyte.
Electrode structures for transdermal drug delivery have an active electrode which delivers the ionic medication and an indifferent electrode with an electrolyte. The active and indifferent electrodes are connected to the skin forming a circuit. The current passes from a power source through one of the electrodes to the skin, through the skin into the subdermal tissue, back out through the skin at a separate location and then through the other electrode. Regulation of the rate of drug delivery has been controlled by the amount of current flow and that has been limited by the electrical resistance or impedance of skin. Skin irritation is directly related to the aggressiveness of the ionic substances at the interface between the electrode and the skin and the electrical power needed to deliver the medication. The desired delivery rate often cannot be tolerated. Various power sources and electrode arrangements and constructions have been suggested to avoid burns and irritation where the iontophoresis takes place.
The efforts to use voltage levels below that required for hydrolysis as in U.S. Pat. No. 4,752,285 or the use of alternating current to eliminate galvanic action are not entirely effective. The ability to deliver the preferred level of medication without skin irritation is a function of many factors which influence the efficiency with which any medication can be iontopheretically delivered at a preferred rate. In the past the configuration of the electrode has not been considered a factor although various electrode configurations have been proposed.
In U.S. Pat. No. 617,543 a hollow roller electrode of any suitable cross section with wooden insulating strips between metallic conducting strips that are alternately connected to opposite sides of a source of electricity. No specific recognition of iontophoresis or disclosure of contact by more than one set of metallic strips with the skin to complete at one time more than one circuit through the skin are disclosed. Exit valves dispense medication, surround the surface of the hollow electrode which contains the medication and open when in contact with the skin.
Batteries are frequently used as a power source because of their portability and since low voltage direct current is effective. In U.S Pat. Nos. 222,276 and 770,014 electrode battery combinations are explained. Battery current drives medication or a conducting salt into the body. Zinc and copper electrodes form the battery and in the 222,276 patent the electrodes are concentric to one another; in the 770,014 patent the electrodes are of similar construction with surfaces which project through separating insulation. The projections may carry absorbent liquid containing pads placed between the projections and the body.
Supports for the electrodes and the power source have also included reservoirs for the ionic medication. The particular configuration of the support is a function of how much of the iontophoretic apparatus is carried in one package. U.S. Pat. Nos. 4,164,226 and 4,211,222 disclose a plurality of alternate electrode elements which are claimed to avoid iontophoretic burn by permitting current to be applied over a period of time. The 4,164,226 patent has small positive and negative electrodes which are spacially intermingled. The size of the positive electrodes may be the same as the negative or may be larger. A thick porous and preferably moist material is used between the negative electrode and the skin to eliminate iontophoretic burn by preventing the migration of particles from the metallic electrode as the current passes into the skin.
Electrode structures wherein the active and the indifferent electrodes are carried on an insulator separate from each other but in position to contact the skin have taken many forms. U.S. Pat. No. 4,325,367 has an electrode support structure on which is mounted a pair of electrodes in proximity to one another and a source of electrical power for the electrodes. U.S. Pat. No. 4,406,658 shows an iontophoresis device with an active electrode from which the ionic substance is driven into the body and an indifferent or ground electrode used to complete the electrical circuit through the body. The ionic substance can be positively or negatively charged but the active electrode must also be positively or negatively charged, respectively. The electrodes in U.S. Pat. No. 4,406,658 patent are adhesive so as to adhere to the skin. The electrodes are held on a support and spaced apart by a projection between them. A battery is also carried in the support and a switch for reversing the polarity of the power supply to the electrodes.
U.S. Pat. No. 4,622,031 has multilayer electrode with a peripheral contact lip as one electrode element surrounding the other electrode element. Current from a battery in that multilayer package drives the ions from the reservoir into the skin; a LED indicates current flow through the lip and into the skin by means of electrical connection to the skin with a conductive adhesive. U.S. Pat. No. 4,640,689 discloses a pair of side by side active and indifferent electrodes. At least two electrode elements are within a cover partially enclosing a reservoir which is in one of the elements. A semi permeable member in one element forms a drug gradient when power is applied from the source through a conductive adhesive to the skin.
Many materials have been suggested and used as conductive electrodes including metallic and porous natural and polymer structures depending upon what drug is desired to be delivered. U.S. Pat. No. 4,708,716 discloses a plurality of cells or reservoir units with flexible separations therebetween to provide flexibility of the electrode to conform to the contours of the body. Each cell or unit is surrounded by a nonconductive gel. U.S. Pat. No. 4,713,050 has a layered electrode construction with a reservoir having a cover, lip and adhesive. U.S. Pat. No. 4,731,926 discloses a method of manufacture of a multi-reservoir device which is layered and lipped in configuration. The method of making the reservoirs includes occluding foam to provide insulators between the reservoirs/elements.
U.S. Pat. No. 4,734,090 discloses techniques recognizing the principle that the sweat ducts have less resistance to the flow of current and therefore ions so as to direct the current to the stratum corneum or to circumvent the stratum corneum or by using a system which plugs the entrances to the ducts. U.S. Pat. No. 4,653,501 shows a electrode construction wherein the metal conductor can be reused and the electrode pad can be replaced such that the more expensive part of the electrode is retained and the body contact part of the electrode is disposable. U.S. Pat. No. 4,416,274 shows an electrode for iontophoresis which has structure to inhibit the migration of ions laterally or in a direction parallel to the surface of the skin in order to decrease the likelihood of burns.
West German Patent DE 3,020,789 discloses a electrode which may be used to deliver medication applied to the body and underneath the electrode such that direct current through the electrode will drive the medication into the body. An adjustable electrode with a slidable support coupling holds adjustably positioned arms for placement of the electrodes in spaced apart relation. Thus current can be applied to different parts of the body and the spacing between the electrodes can be adjusted. International patent application W088/00846 discloses an electrode which can be carried on a wrist belt.
Missing from these patents is the fundamental concept of having multiple active and indifferent elements separated by an insulator wherein the spacing of the elements provides electric field lines located for transdermally delivering drug to a required depth. The unappreciated advantages of such multiple elements are improved power efficiency and the discovery that the amount of separation of the elements relates to the penetration depth of the iontophoretic delivery of medication. Improved power efficiency and the relationship of electrode spacing to depth of drug delivery result from placement of the active and indifferent elements against an insulator which sets the spacing and accordingly the depth of iontophoretic transdermal penetration.